Treatment of tuberculosis: guidelines for national programmes

Summary

The guidelines

The World Health Organization’s Stop TB Department has prepared this fourth edition of Treatment of tuberculosis: guidelines, adhering fully to the new WHO process for evidence-based guidelines. Several important recommendations are being promoted in this new edition.

First, the recommendation to discontinue the regimen based on just 2 months of rifampicin (2HRZE/6HE) and change to the regimen based on a full 6 months of rifampicin (2HRZE/4HR) will reduce the number of relapses and failures. This will alleviate patient suffering resulting from a second episode of tuberculosis (TB) and conserve patient and programme resources.

Second, this fourth edition confirms prior WHO recommendations for drug susceptibility testing (DST) at the start of therapy for all previously treated patients. Finding and treating multidrug-resistant TB (MDR-TB) in previously treated patients will help to improve the very poor outcomes in these patients. New recommendations for the prompt detection and appropriate treatment of (MDR-TB) cases will also improve access to life-saving care. The retreatment regimen with first-line drugs (formerly called “Category 2” regimen) is ineffective in MDR-TB; it is therefore critical to detect MDR-TB promptly so that an effective regimen can be started.

Third, detecting MDR-TB will require expansion of DST capacity within the context of country-specific, comprehensive plans for laboratory strengthening. This fourth edition provides guidance for treatment approaches in the light of advances in laboratory technology and the country’s progress in building laboratory capacity. In countries that use the new rapid molecular-based tests, DST results for rifampicin/isoniazid will be available within 1‒2 days and can be used in deciding which regimen should be started for the individual patient. Rapid tests eliminate the need to treat “in the dark” during the long wait for results of DST by other methods (weeks for liquid media methods or months for solid media methods).

Because of the delays in obtaining results, this new edition recommends that countries using conventional DST methods should start treatment with an empirical regimen. If there is a high likelihood of MDR-TB, empirical treatment with an MDR regimen is recommended until DST results are available. Drug resistance surveillance (DRS) data or surveys will be required to identify subgroups of TB patients with the highest prevalence of MDR-TB, such as those whose prior treatment has failed. Implementation of these recommendations will require every country to include an MDR-TB regimen in its standards for treatment in collaboration with the Green Light Committee Initiative.

Fourth, diagnosing MDR-TB cases among previously treated patients and providing effective treatment will greatly help in halting the spread of MDR-TB. This edition also addresses the prevention of acquired MDR-TB, especially among new TB patients who already have isoniazid-resistant Mycobacterium tuberculosis when they start treatment. The meta-analyses that form the evidence base for this revision revealed that new patients with isoniazid-resistant TB have a greatly increased risk of acquiring additional drug resistance. To prevent amplification of existing drug resistance, this edition includes the option of adding ethambutol to the continuation phase of treatment for new patients in populations with high prevalence of isoniazid resistance. In addition, the daily dosing recommended for the intensive phase may also help in reducing acquired drug resistance, especially in patients with pretreatment isoniazid resistance.

Finally, this edition strongly reaffirms prior recommendations for supervised treatment, as well as the use of fixed-dose combinations of anti-TB drugs and patient kits as further measures for preventing the acquisition of drug resistance.

Use of the new WHO process for evidence-based guidelines revealed many key unanswered questions. What is the best way to treat isoniazid-resistant TB and prevent MDR? What is the optimal duration of TB treatment in HIV-positive patients? Which patients are most likely to relapse and how can they be detected and treated? Identification of such crucial questions for the future research agenda is an important outcome of this revision and will require careful follow-up to ensure that answers will be provided to further strengthen TB care practices.

As new studies help to fill these gaps in knowledge, new laboratory technology is introduced, and new drugs are discovered, these guidelines will be updated and revised. In the meantime, WHO pledges its full support to helping countries to implement and evaluate this fourth edition of "Treatment of tuberculosis: guidelines" and to use the lessons learnt to improve access to high-quality, life-saving TB care.